Binding of factor VIIa (VIIa) to tissue factor (TF) triggers the coagulation cascade. Several studies indicate a possible role for TF-VIIa in other cellular functions, in addition to coagulation, under pathophysiological conditions. Recent studies suggest that TF-VIIa mediates cell signaling by two distinct mechanisms, TF cytoplasmic domain-dependent and TF-VIIa protease activity-dependent. In this review, we focus upon TF-VIIa protease-induced gene expression and how the altered gene expression could potentially affect various cellular processes.